1,721,042 research outputs found
Genetica delle forme familiari comuni e rare di diabete mellito
No full textBackground. L’esperienza clinica quotidiana c’insegna che alcuni pazienti adulti che vengono diagnosticati come affetti da diabete mellito tipo 2 (DMT2) presentano una forma multigenerazionale di diabete che manca ancora di una precisa definizione clinica e molecolare.
Obiettivo. L’obiettivo principale di questo studio è stato quello di identificare, all’interno di una coorte d’individui già diagnosticati come DMT2, quei pazienti che erano in realtà affetti da una forma di diabete multigenerazionale, indipendente da mutazioni responsabili del Diabete giovanile dell’adulto (Maturity Onset Diabetes of the Young: MODY) o del Diabete Mitocondriale associato a sordità (Maternally Inherited Diabetes and Deafness: MIDD). Grazie a strategie di sequenziamento di nuova generazione, abbiamo analizzato il DNA di tali pazienti per determinare l’architettura genetica che sottende tale forma di diabete. Infine, ci siamo concentrati sulla determinazione delle caratteristiche cliniche di tali pazienti, per poi confrontarle con quelle di pazienti affetti da MODY o dal tradizionale DMT2.
Materiali e metodi. All'interno di un campione di 2,583 pazienti precedentemente diagnosticati come affetti da DMT2, sono stati selezionati quei pazienti che appartenevano a famiglie affette da diabete in almeno tre generazioni consecutive. I DNA dei soggetti identificati sono stati raccolti e sequenziati inizialmente con il metodo di Sanger, e successivamente attraverso le moderne tecniche del Targeted Resequencing, con lo scopo di individuare mutazioni in geni associati a forme di diabete monogenico come il MODY o il Diabete Neonatale (DN), e del Whole Exome Sequencing (WES), per identificare mutazioni in geni mai associati al diabete.
Risultati. Abbiamo osservato che il 2.6% di un campione di 2,583 pazienti precedentemente diagnosticati per il DMT2 era rappresentato da famiglie affette da una forma di diabete multigenerazionale che abbiamo proposto di definire FDA (Familial Diabetes of the Adulthood). In seguito all’analisi genetica compiuta attraverso il sequenziamento di Sanger ed il Targeted Resequencing su tali famiglie, è risultato che 6,7 e 1 famiglia riportavano mutazioni rispettivamente in geni MODY, DN e MODY + DN, mentre il sequenziamento degli esomi, compiuto tramite WES, ci ha premesso di identificare due mutazioni nel gene APPL1 che causano iperglicemia in due di tali famiglie. In seguito al confronto tra le caratteristiche cliniche di questi pazienti con quelle di 1,028 pazienti affetti dal DMT2, è risultato che l’FDA si caratterizza per un’età alla diagnosi più precoce (p<0.001). In 118 pazienti FDA e 838 pazienti DMT2 il tasso d’incidenza della mortalità generale è risultato simile: 1.93 contro 1.89 eventi/100 anni-persona.
Conclusioni. Con questo studio abbiamo caratterizzato un gruppo di pazienti affetti da una forma di diabete familiare multigenerazionale che abbiamo proposto di definire FDA. Tali pazienti si distinguevano da quelli affetti dal tradizionale DMT2 per l’età alla diagnosi più precoce, tuttavia non implicando alcun effetto sul tasso d’incidenza della mortalità generale che è risultato simile nei due gruppi. Attraverso la tecnica del Targeted Resequencing abbiamo osservato che l’FDA è geneticamente eterogeneo, essendo costituito da mutazioni in geni MODY (24%), mutazioni in geni associati al DN (13%) e mutazioni in geni MODY + DN (2%). Il restante 61% dell’ereditabilità dell’FDA è stato investigato tramite il sequenziamento degli esomi (WES) di tali soggetti attraverso cui abbiamo identificato un nuovo gene-malattia (APPL1), dimostrando come tale approccio, applicato alle famiglie FDA, rappresenti una buona strategia per la scoperta di nuove vie di segnale o metaboliche che modulano l’omeostasi del glucosio e, quindi, il rischio di diabete
Parkinsonism and severe hypothyroidism in an elderly patient: a case of lithium toxicity due to pharmacological interactions
No full textAbstract
WHAT IS KNOWN AND OBJECTIVE:
Hypothyroidism is a common clinical side effect of lithium treatment, whereas parkinsonism is a very rare adverse event. A number of case series of clinical signs of reversible and permanent parkinsonism due to lithium toxicity have been previously published, but never in association with hypothyroidism. We describe a rare clinical case of concurrent reversible parkinsonism and severe hypothyroidism due to lithium toxicity.
CASE SUMMARY:
The patient was a 74-year-old woman chronically treated with carbonate lithium (300 mg, twice daily) and clomipramine (75 mg, once daily); she also received valsartan (160 mg) plus hydrochlorothiazide (12·5 mg), once daily. The patient was visited after a 1-week history of progressively worsening and disabling parkinsonism. Laboratory tests showed elevated values of lithium and thyroid stimulating hormone (TSH) serum concentrations as well as reduced circulating thyroid hormone serum concentrations. Lithium treatment was discontinued; treatment with levothyroxine and saline solution i.v. was readily performed, and valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once daily). Within a few days, the patient showed a rapid improvement in overall clinical condition, but complete resolution of neurologic symptoms occurred only after about 5 months.
WHAT IS NEW AND CONCLUSION:
Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicit
Measuring frailty in population-based healthcare databases: multi-dimensional prognostic indices for the improvement of geriatric care
Full text linkThe prognostic evaluation of geriatric patients is critical in helping clinicians to weigh the risks versus the benefits of available therapeutic options. Frailty contributes significantly to the risk of mortality in older patients and is already known to have implications on the outcome of treatment in a clinical context. The multi-dimensional prognostic index (MPI) is a prognostic tool based on a comprehensive geriatric assessment and includes detailed information on patient cognition, functionality, disease and drug burden. The value of the MPI in predicting mortality has already been shown in hospital and community settings but never in a population- based healthcare database setting. One of the aims of the ongoing EU-funded MPI_Age project is to improve our understanding of how geriatric frailty data can be identified in healthcare databases and whether this can be used to predict serious adverse events associated with pharmacotherapy. Our findings suggest that data on functionality in elderly patients is poorly registered in The Health Improvement Network (THIN), a UK nationwide general practice database, and only few of the functionality domains could be used in a population-based analysis. The most commonly registered functionality information was related to mobility, dressing, accommodation and cognition. Our results suggest that some of these functionality domains are predictive of short- and long-term mortality in community-dwelling patients. This may have implications in observational research where frailty is an unmeasured confounder
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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